Franck Morel

L’emploi des seniors se porte mieux mais il se situe toujours à un niveau insuffisant, en particulier par rapport à nos voisins européens. Il est essentiel à la soutenabilité de notre régime de retraite, que la réforme adoptée cette année veut permettre.

Sugar-based molecules such as heparins or natural heparan sulfate polysaccharides have been developed and widely studied for controlling heparanase (HPSE) enzymatic activity, a key player in extracellular matrix remodelling during cancer pathogenesis. However, non-enzymatic functions of HPSE have also been described in tumour mechanisms. Given their versatile properties, we hypothesized that sugar-based inhibitors may interfere with enzymatic but also non-enzymatic HPSE activities. In this work, we assessed the effects of an original marine λ-carrageenan derived oligosaccharide (λ-CO) we previously described, along with those of its native counterpart and heparins, on cell viability, proliferation, migration, and invasion of MDA-MB-231 breast cancer cells but also of sh-MDA-MB-231 cells, in which the expression of HPSE was selectively downregulated. We observed no cytotoxic and no anti-proliferative effects of our compounds but surprisingly λ-CO was the most efficient to reduce cell migration and invasion compared with heparins, and in a HPSE-dependent manner. We provided evidence that λ-CO tightly controlled a HPSE/MMP-14/MMP-2 axis, leading to reduced MMP-2 activity. Altogether, this study highlights λ-CO as a potent HPSE “modulator” capable of reducing not only the enzymatic activity of HPSE but also the functions controlled by the HPSE levels.

Selective laser melting SLM is investigated through a study of redesign and characterization of an aeronautic part made of titanium Ti6Al4V. The part must ensure an excellent static and fatigue behaviour. The methodology developed hereby follows 3 main steps: First, the influence of laser power, laser speed and hatch distance on the amount/rate of porosity is performed to define optimized process parameters. Then, the influence of building process strategy, i.e. building direction or as-built surface roughness on the static and fatigue behaviour are studied and understood by following a vast experimental campaign. Obtained properties are finally used in a topology optimization study to find the best compromise between part weight and fatigue behavior . 3 prototypes of simulated part are produced and then characterized. Fatigue tests are conducted on the component and confirm the fatigue design proposed. Obtained results are encouraging and illustrate the fatigue design optimization of a complex Additive Manufacturing component.

Background: A relationship between alcohol consumption and psoriasis has been reported, but it is unclear whether alcohol consumption aggravates psoriasis. Here, we studied the effect of chronic ethanol (EtOH) consumption in the murine model of Aldara‐induced psoriasiform dermatitis.Methods: C57BL/6 mice received 5% EtOH in their drinking water for 10 weeks. Dermatitis was induced from weeks 9 to 10, by applying Aldara to the shaved patch of skin on the back. Inflammation was characterized by histological and transcriptomic analyses.Results: EtOH consumption aggravated Aldara‐induced dermatitis. The scales were more severe, epidermal thickening was more pronounced, and cutaneous expression of Th17‐related cytokines was exacerbated. Control mice simply receiving EtOH displayed minimal cutaneous inflammation, characterized by epidermal infiltrates of T lymphocytes and the overexpression of IL‐17A and the Th17‐recruiting chemokine CCL20. In vitro studies showed that low concentrations of EtOH induce the expression of CCL20 by murine epidermal keratinocytes.Conclusion: Alcohol consumption leads to subliminar skin inflammation, which is revealed by the exacerbation of Aldara‐induced experimental psoriasiform dermatitis, likely through Th17‐type minimal skin inflammation. These results favor the systematic management of alcohol consumption in psoriatic patients.

Loss of melanocytes is the pathological hallmark of vitiligo, a chronic inflammatory skin depigmenting disorder induced by exaggerated immune response, including autoreactive CD8 T cells producing high levels of type 1 cytokines. However, the interplay between this inflammatory response and melanocyte disappearance remains to be fully characterized. Here, we demonstrate that vitiligo skin contains a significant proportion of suprabasal melanocytes, associated with disruption of E-cadherin expression, a major protein involved in melanocyte adhesion. This phenomenon is also observed in lesional psoriatic skin. Importantly, apoptotic melanocytes were mainly observed once cells were detached from the basal layer of the epidermis, suggesting that additional mechanism(s) could be involved in melanocyte loss. The type 1 cytokines IFN-γ and TNF-α induce melanocyte detachment through E-cadherin disruption and the release of its soluble form, partly due to MMP-9. The levels of MMP-9 are increased in the skin and sera of patients with vitiligo, and MMP-9 is produced by keratinocytes in response to IFN-γ and TNF-α. Inhibition of MMP-9 or the JAK/STAT signaling pathway prevents melanocyte detachment in vitro and in vivo. Therefore, stabilization of melanocytes in the basal layer of the epidermis by preventing E-cadherin disruption appears promising for the prevention of depigmentation occurring in vitiligo and during chronic skin inflammation.